Abstract
Zika virus (ZIKV) is a re-emerged flavivirus transmitted by Aedes spp mosquitoes that has caused outbreaks of fever and rash on islands in the Pacific and in the Americas. These outbreaks have been associated with neurologic complications that include congenital abnormalities and Guillain-Barré syndrome (GBS). The pathogenesis of ZIKV-associated GBS, a potentially life-threatening peripheral nerve disease, remains unclear. Because Schwann cells (SCs) play a central role in peripheral nerve function and can be the target for damage in GBS, we characterized the interactions of ZIKV isolates from Africa, Asia and Brazil with human SCs in comparison with the related mosquito-transmitted flaviviruses yellow fever virus 17D (YFV) and dengue virus type 2 (DENV2). SCs supported sustained replication of ZIKV and YFV, but not DENV. ZIKV infection induced increased SC expression of IL-6, interferon (IFN)β1, IFN-λ, IFIT-1, TNFα and IL-23A mRNAs as well as IFN-λ receptors and negative regulators of IFN signaling. SCs expressed baseline mRNAs for multiple potential flavivirus receptors and levels did not change after ZIKV infection. SCs did not express detectable levels of cell surface Fcγ receptors. This study demonstrates the susceptibility and biological responses of SCs to ZIKV infection of potential importance for the pathogenesis of ZIKV-associated GBS.
Highlights
Zika virus (ZIKV) is a plus-strand enveloped RNA virus that belongs to the genus Flavivirus and is related to other mosquito-borne flaviviruses, including dengue, yellow fever, West Nile, Japanese encephalitis and Spondweni viruses[1]
To determine susceptibility of human Schwann cells (hSCs) to flavivirus infection, cells were incubated (MOI = 5) with yellow fever virus 17D (YFV) 17D, dengue virus type 2 (DENV2) and three strains of ZIKV: 1968 Nigeria, 2014 Thailand and 2015 Brazil (Fortaleza) chosen to represent the historical shifts of ZIKV as it moved from Africa to Asia and the Americas[37]
YFV 17D replicated in hSCs, but DENV2 infection resulted in little virus production (Fig. 1B)
Summary
Zika virus (ZIKV) is a plus-strand enveloped RNA virus that belongs to the genus Flavivirus and is related to other mosquito-borne flaviviruses, including dengue, yellow fever, West Nile, Japanese encephalitis and Spondweni viruses[1]. The first recognized large outbreak of human ZIKV infection occurred in 2007 on the Pacific island of Yap, in the Federated States of Micronesia[10]. In May 2015, locally acquired ZIKV disease was recognized in Brazil[12] followed by rapid spread through the Americas and Caribbean islands with accompanying reports of neurological complications and congenital malformations including microcephaly[13,14,15]. The first association of ZIKV infection with Guillain-Barré syndrome (GBS) was a retrospective study of the French Polynesian outbreak where there was a 20-fold increase in GBS incidence and all of the 42 patients hospitalized with GBS had anti-ZIKV antibody[16]. GBS, a potentially life-threatening peripheral nerve disease, is characterized by a rapid onset of bilateral weakness progressing to paralysis that may be accompanied by sensory symptoms. In AMAN, membranes of the nerve axon are the primary targets of cross-reactive anti-ganglioside antibodies while in AIDP the Schwann cell (SC)-produced myelin sheath is the target for damage but the relative roles and specificities of antibody and cellular immune responses are unclear[20]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
